title: Proteomic and metabolomic analysis of H2O2-induced premature senescent human mesenchymal stem cells.
abstract: Stress induced premature senescence (SIPS) occurs after exposure to many different sublethal stresses including H(2)O(2), hyperoxia, or tert-butylhydroperoxide. Human mesenchymal stem cells (hMSCs) exhibit limited proliferative potential in vitro, the so-called Hayflick limit. According to the free-radical theory, reactive oxygen species (ROS) might be the candidates responsible for senescence and age-related diseases. H(2)O(2) may be responsible for the production of high levels of ROS, in which the redox balance is disturbed and the cells shift into a state of oxidative stress, which subsequently leads to premature senescence with shortening telomeres. H(2)O(2) has been the most commonly used inducer of SIPS, which shares features of replicative senescence (RS) including a similar morphology, senescence-associated β-galactosidase activity, cell cycle regulation, etc. Therefore, in this study, the senescence of hMSC during SIPS was confirmed using a range of different analytical methods. In addition, we determined five differentially expressed spots in the 2-DE map, which were identified as Annexin A2 (ANXA2), myosin light chain 2 (MLC2), peroxisomal enoyl-CoA hydratase 1 (ECH1), prosomal protein P30-33K (PSMA1) and mutant β-actin by ESI-Q-TOF MS/MS. Also, proton ((1)H) nuclear magnetic resonance spectroscopy (NMR) was used to elucidate the difference between metabolites in the control and hMSCs treated with H(2)O(2). Among these metabolites, choline and leucine were identified by (1)H-NMR as up-regulated metabolites and glycine and proline were identified as down-regulated metabolites.
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
authors.forename: Ji-Soo
authors.initials: JS
authors.lastname: Kim
authors.forename: Eui-Jin
authors.initials: EJ
authors.lastname: Kim
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Yang
authors.forename: Geum-Sook
authors.initials: GS
authors.lastname: Hwang
authors.forename: Chan-Wha
authors.initials: CW
authors.lastname: Kim
mesh_terms: D017306:Annexin A2 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D002794:Choline / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005998:Glycine / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007930:Leucine / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D055432:Metabolomics; D011392:Proline / Q000378:metabolism; D040901:Proteomics; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017306:Annexin A2; D017382:Reactive Oxygen Species; D011392:Proline; D006861:Hydrogen Peroxide; D007930:Leucine; D002794:Choline; D005998:Glycine